Dilated cardiomyopathy: remodelling, risk stratification and personalising therapy
File(s)
Author(s)
Halliday, Brian P.
Type
Thesis
Abstract
Introduction: Dilated cardiomyopathy (DCM) is a common heterogeneous disease with variable outcomes. Unmet needs include the improvement of risk stratification, particularly in patients with mild and moderately reduced left ventricular ejection fraction (LVEF). It is also unclear whether DCM patients with improved LVEF simply have remission of disease or have permanently recovered. The benefit of continued therapy is unclear.
Methods & Results: We investigated the use of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) in the risk stratification of patients with DCM in a large registry. The presence of mid-wall LGE was associated with a nine-fold increase in the risk of SCD events in patients with mild and moderately reduced LVEF. In a study, including patients of all disease severities, the presence of septal LGE was most strongly associated with all-cause mortality whilst septal and left ventricular free-wall enhancement was associated with the greatest risk of SCD events. For both end-points, even small degrees of LGE were associated with large increases in risk. We also demonstrated that women with DCM have markers of less severe disease and reduced adjusted all-cause mortality compared to men with the disease.
In addition, the safety and feasibility of heart failure therapy withdrawal in DCM patients with improved LVEF, normal left ventricular cavity size and low natriuretic peptide concentration was investigated in a randomised controlled trial. The preliminary results of the first 35 patients enrolled demonstrated that 41.2% of patients suffered a relapse within 6 months of starting therapy withdrawal compared to none of the patients in the control arm.
Conclusions: LGE-CMR can identify patients at risk of SCD. Women with DCM have better outcomes compared to men. At least a proportion of patients with improved LVEF continue to benefit from therapy. Routine withdrawal of therapy in this group is unwise.
Methods & Results: We investigated the use of late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) in the risk stratification of patients with DCM in a large registry. The presence of mid-wall LGE was associated with a nine-fold increase in the risk of SCD events in patients with mild and moderately reduced LVEF. In a study, including patients of all disease severities, the presence of septal LGE was most strongly associated with all-cause mortality whilst septal and left ventricular free-wall enhancement was associated with the greatest risk of SCD events. For both end-points, even small degrees of LGE were associated with large increases in risk. We also demonstrated that women with DCM have markers of less severe disease and reduced adjusted all-cause mortality compared to men with the disease.
In addition, the safety and feasibility of heart failure therapy withdrawal in DCM patients with improved LVEF, normal left ventricular cavity size and low natriuretic peptide concentration was investigated in a randomised controlled trial. The preliminary results of the first 35 patients enrolled demonstrated that 41.2% of patients suffered a relapse within 6 months of starting therapy withdrawal compared to none of the patients in the control arm.
Conclusions: LGE-CMR can identify patients at risk of SCD. Women with DCM have better outcomes compared to men. At least a proportion of patients with improved LVEF continue to benefit from therapy. Routine withdrawal of therapy in this group is unwise.
Version
Open Access
Date Issued
2018-04
Date Awarded
2018-09
Advisor
Prasad, Sanjay
Cleland, John
Sponsor
British Heart Foundation
Grant Number
FS/15/29/31492
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)